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Updated: Jun 19, 2026
Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
Diacerein reduces inflammasome activation and SARS-CoV-2 virus replication: a proof-of-concept translational study
Helison R P Carmo1, Alejandro Rossel Castillo1, Isabella Bonilha1
1Laboratory of Vascular Biology and Atherosclerosis (Aterolab), State University of Campinas (UNICAMP), Campinas, Brazil.
Background:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is linked to high mortality, primarily through an intense inflammatory response. Diacerein has emerged as a potential therapy for COVID-19 due to its potential impact in decreasing the inflammasome activation and coronavirus replication. This study aims to explore diacerein's influence in inhibiting both viral replication and the inflammatory response after SARS-CoV-2 infection.
Methods:
Human peripheral blood mononuclear cells (PBMCs) were obtained from healthy volunteers and infected in vitro with SARS-CoV-2. Additionally, we carried out a pilot randomized, double-blind, placebo-controlled study with 14 participants allocated to diacerein (n = 7) or placebo (n = 7) therapies every 12 h for 10 days. The primary endpoint was change in plasma markers of inflammasome activation (NLRP3, caspase-1, and gasdermin-D).
Results:
In vitro protocols have shown that rhein, diacerein's primary metabolite, decreased IL-1β secretion caused by SARS-CoV-2 infection in human PBMCs (p < 0.05), and suppressed viral replication when administered either before or after the virus incubation (p < 0.05). This later effect was, at least partially, attributed to its inhibitory effect on 3-chymotrypsin-like protease (SARS-CoV-2 3CLpro) and papain-like protease in the SARS-CoV-2 (SARS-CoV-2 PLpro) virus and in the phosphorylation of proteins related cytoskeleton network (p < 0.05). Diacerein-treated COVID-19 patients presented a smaller area under the curve for NLRP3, caspase-1 and GSDM-D measured on days 2, 5, and 10 after hospitalization compared to those receiving a placebo (p < 0.05).
Conclusion:
The indicated mechanisms of action of diacerein/rhein can reduce viral replication and mitigate the inflammatory response related to SARS-CoV-2. These findings are preliminary and require confirmation in clinical trials.
Insights
Diacerein and its metabolite Rhein show promise in combating COVID-19 by inhibiting SARS-CoV-2 replication and reducing harmful inflammation. This study indicates diacerein
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with high mortality, largely due to an overactive inflammatory response.
- Diacerein is being investigated for its potential to treat COVID-19 by targeting inflammasome activation and viral replication.
Purpose of the Study:
- To investigate the efficacy of diacerein in inhibiting SARS-CoV-2 replication.
- To evaluate diacerein's impact on reducing the inflammatory response in SARS-CoV-2 infected individuals.
Main Methods:
- Human peripheral blood mononuclear cells (PBMCs) were infected in vitro with SARS-CoV-2.
- A pilot randomized, double-blind, placebo-controlled trial was conducted with 14 participants receiving either diacerein or a placebo for 10 days.
- Plasma markers of inflammasome activation (NLRP3, caspase-1, gasdermin-D) were measured as primary endpoints.
Main Results:
- In vitro, diacerein's metabolite Rhein reduced IL-1β secretion and suppressed SARS-CoV-2 replication by inhibiting key viral proteases (3CLpro and PLpro).
- Rhein also affected the phosphorylation of cytoskeleton-related proteins.
- Diacerein treatment in COVID-19 patients led to lower levels of NLRP3, caspase-1, and GSDM-D compared to placebo.
Conclusions:
- Diacerein and Rhein exhibit mechanisms that can decrease viral load and mitigate SARS-CoV-2-induced inflammation.
- These preliminary findings suggest diacerein as a potential therapeutic agent for COVID-19.
- Further clinical trials are necessary to confirm these results.
